RECIST/CA-125 progression-free survival and the role of CA-125 surveillance in the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian carcinoma

Objectives: In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; P<0.001; median PFS 22.1 vs 16.6 months) (Ray-Coquard et al. NEJM 2019). Limited evidence supports use of serum CA-125, a surrogate biomarker for progression, to detect relapse in pts receiving PARP inhibitor maintenance therapy. We evaluated RECIST/CA-125 progression and CA-125 surveillance in PAOLA-1. Methods: Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. Results: Conclusions: Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, tBRCAm pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy. In the PAOLA-1/ENGOT-ov25 primary analysis (NCT02477644), adding the PARP inhibitor olaparib to maintenance bevacizumab (bev) after first-line platinum-based chemotherapy with bev led to a significant progression-free survival (PFS) benefit vs placebo (pbo) + bev in patients (pts) with advanced high-grade ovarian cancer (HGOC), using modified RECIST v1.1 criteria (HR 0.59; 95% CI 0.49-0.72; P<0.001; median PFS 22.1 vs 16.6 months) (Ray-Coquard et al. NEJM 2019). Limited evidence supports use of serum CA-125, a surrogate biomarker for progression, to detect relapse in pts receiving PARP inhibitor maintenance therapy. We evaluated RECIST/CA-125 progression and CA-125 surveillance in PAOLA-1. Pts with newly diagnosed, FIGO stage III-IV HGOC in response after platinum-based chemotherapy plus bev received bev (15 mg/kg q3w for 15 months) + olaparib (300 mg bid for 24 months) or pbo. Scans were performed every 24 weeks, or every 12 weeks if there was evidence of clinical or CA-125 progression. CA-125 levels were assessed every 12 weeks. Time to RECIST or CA-125 progression or death was a secondary endpoint; RECIST/CA-125 progression by biomarker status, response to initial therapy and CA-125 level at baseline were explored. Median PFS and HRs were consistent when progression was assessed by either RECIST or RECIST/CA-125 in PAOLA-1. Scans appear particularly important for detecting progression in HRD-positive pts, tBRCAm pts or pts with normal CA-125 levels at baseline as CA-125 levels did not seem to predict relapse in these pts. Results suggest that CA-125 surveillance alone may be sufficient to detect progression in most pts with abnormal baseline CA-125 levels when starting maintenance therapy.